Herpesviruses are relatively common causes of infections in immunosuppressed patients such as cancer or transplant patients, and certain herpesviruses have been shown to cause neoplasias. Herpes simplex virus type 2 (HSV-2) has been associated with cervical carcinoma in humans and mice. In this research program, we plan to evaluate the relative roles and interactions among components of the immune system (cellular immunity, antibody, macrophage activity, interferon) to acute infection of female mice with HSV-2 inoculated by the intravaginal route. We have shown that mice depleted of thymus derived lymphocytes (TXB mice) are approximately 10 times more susceptible to HSV-2 than are normal age-matched controls. However, treatment of either normal or TXB mice with the immunopotentiator pyran protects mice against the lethal effects of HSV-2 infection. Thus the immunopotentiator may exert antiviral activity independent of thymus derived lymphocytes. Experiments to delineate the role of the macrophage in this resistance are currently in progress.